Some medical devices, including implanted analyte sensors, drug delivery devices and cell transplantation devices require close vascularization and transport of solutes across the device-tissue interface for proper function. These devices generally include a biointerface membrane, which encases the device or a portion of the device to prevent access by host inflammatory cells, immune cells, or soluble factors to sensitive regions of the device.
A disadvantage of conventional implantable devices is that they often stimulate a local inflammatory response, called the foreign body response (FBR), which has long been recognized as limiting the function of implantable devices that require solute transport. The FBR has been well described in the literature.
FIG. 1 is a schematic drawing that illustrates a classical FBR to a conventional implantable device 10 implanted under the skin. There are three main layers of a FBR. The innermost FBR layer 12, adjacent to the device, is composed generally of macrophages and foreign body giant cells 14 (herein referred to as the barrier cell layer). These cells form a monolayer of closely opposed cells over the entire surface of a membrane on the implantable device. The relatively smooth surface of the membrane causes the downward tissue contracture 21 to translate directly to the cells at the device-tissue interface 26. The intermediate FBR layer 16 (herein referred to as the fibrous zone), lying distal to the first layer with respect to the device, is a wide zone (about 30-100 microns) composed primarily of fibroblasts 18, contractile fibrous tissue 20. The organization of the fibrous zone, and particularly the contractile fibrous tissue 20, contributes to the formation of the monolayer of closely opposed cells due to the contractile forces 21 around the surface of the foreign body (for example, device 10). The outermost FBR layer 22 comprises loose connective granular tissue containing new blood vessels 24.
Over time, this FBR tissue becomes muscular in nature and contracts around the foreign body so that the foreign body remains tightly encapsulated. Accordingly, the downward forces 21 press against the device-tissue interface 26, and without any counteracting forces, aid in the formation of a barrier cell layer 14 that blocks and/or refracts the transport of analytes 23 (for example, glucose) across the device-tissue interface 26.
A consistent feature of the innermost layers 12, 16 is that they are devoid of blood vessels. This has led to widely supported speculation that poor transport of molecules across the device-tissue interface 26 is due to a lack of vascularization near the interface. See Scharp et al., World J. Surg., 8:221-229 (1984); and Colton and Avgoustiniatos, J. Biomech. Eng., 113:152-170 (1991).
The known art purports to increase the local vascularization in order to increase solute availability. However, it has been observed that once the monolayer of cells (barrier cell layer) is established adjacent to a membrane, increasing angiogenesis is not sufficient to increase transport of molecules such as glucose and oxygen across the device-tissue interface 26. In fact, the barrier cell layer blocks and/or refracts the analytes 23 from transport across the device-tissue interface 26. Materials or membranes employed in implantable devices are described in Brauker et al. (U.S. Pat. No. 5,741,330), Seare, Jr. (U.S. Pat. No. 5,681,572), and Picha (U.S. Pat. No. 5,564,439).